Stefano Sdringola

Anatomic versus physiologic assessment of coronary artery disease. Role of coronary flow reserve, fractional flow reserve, and positron emission tomography imaging in revascularization decision-making.

Angiographic severity of coronary artery stenosis has historically been the primary guide to revascularization or medical management of coronary artery disease. However, physiologic severity defined by coronary pressure and/or flow has resurged into clinical prominence as a potential, fundamental change from anatomically to physiologically guided management. This review addresses clinical coronary physiology-pressure and flow-as clinical tools for treating patients. We clarify the basic concepts that hold true for whatever technology measures coronary physiology directly and reliably, here focusing on positron emission tomography and its interplay with intracoronary measurements.

Frequent Diagnostic Errors in Cardiac PET/CT Due to Misregistration of CT Attenuation and Emission PET Images: A Definitive Analysis of Causes, Consequences, and Corrections

Cardiac PET combined with CT is rapidly expanding despite artifactual defects and false-positive results due to misregistration of PET and CT attenuation correction data—the frequency, cause, and correction of which remain undetermined. Methods: Two hundred fifty-nine consecutive patients underwent diagnostic rest–dipyridamole myocardial perfusion PET/CT using 82Rb, a 16-slice PET/CT scanner, helical CT attenuation correction with breathing and also at end-expiratory breath-hold, and averaged cine CT data during breathing. Misregistration on superimposed PET/CT fusion images was objectively measured in millimeters and correlated with associated quantitative size and severity of PET defects. Misregistration artifacts were defined as PET defects with corresponding misregistration on helical CT-PET fusion images that resolved after correct coregistration using a repeat CT scan, cine CT averaged attenuation during normal breathing, or shifted cine CT data that coregistered with PET data. Results: Misregistration of standard helical CT PET images caused artifactual PET defects in 103 of 259 (40%) patients that were moderate to severe in 59 (23%) (P = 0.0000) and quantitatively normalized on cine or shifted cine CT PET (P = 0.0000). Quantitative misregistration was a powerful predictor of artifact size and severity (P = 0.0000), particularly for transaxial misregistration >6 mm occurring in anterior or lateral areas in 76%, in inferior areas in 16%, and at the apex in 8% of 103 artifactual defects. Conclusion: Misregistration of helical CT attenuation and PET emission images causes artifactual defects with false-positive results in 40% of patients that normalize on cine CT PET using averaged CT attenuation data during normal breathing comparable to normal breathing during PET emission scanning and shifting cine CT images to coregister visually with PET.

Frequency and Clinical Implications of Fluid Dynamically Significant Diffuse Coronary Artery Disease Manifest as Graded, Longitudinal, Base-to-Apex Myocardial Perfusion Abnormalities by Noninvasive Positron Emission Tomography

BACKGROUND Diffuse coronary atherosclerosis is the substrate for plaque rupture and coronary events. Therefore, in patients with mild arteriographic coronary artery disease without significant segmental dipyridamole-induced myocardial perfusion defects, we tested the hypothesis that fluid dynamically significant diffuse coronary artery narrowing is frequently manifest as a graded, longitudinal, base-to-apex myocardial perfusion abnormality by noninvasive PET. METHODS AND RESULTS In this study, 1001 patients with documented coronary artery disease by coronary arteriography showing any visible coronary artery narrowing underwent rest-dipyridamole PET perfusion imaging. Quantitative severity of dipyridamole-induced, circumscribed, segmental PET perfusion defects was objectively measured by automated software as the minimum quadrant average relative activity indicating localized flow limiting stenoses. Quantitative severity of the graded, longitudinal, base-to-apex myocardial perfusion gradient indicating fluid dynamic effects of diffuse coronary artery narrowing was objectively measured by automated software as the spatial slope of relative activity along the cardiac longitudinal axis. CONCLUSIONS In patients with mild arteriographic disease without statistically significant dipyridamole-induced segmental myocardial perfusion defects caused by flow-limiting stenoses compared with normal control subjects, there was a graded, longitudinal, base-to-apex myocardial perfusion gradient significantly different from normal control subjects (P=0. 001) that was also observed for moderate to severe dipyridamole-induced segmental perfusion defects (P=0.0001), indicating diffuse disease underlying segmental perfusion defects; 43% of patients with or without segmental perfusion defects demonstrated graded, longitudinal, base-to-apex perfusion abnormalities beyond +/-2 SD of normal control subjects, indicating diffuse coronary arterial narrowing by noninvasive PET perfusion imaging.

Oral acetylcysteine does not protect renal function from moderate to high doses of intravenous radiographic contrast.

The use of radiographic contrast during cardiac catheterization can cause acute renal failure with an increase in morbidity and mortality. Prophylactic acetylcysteine plus intravenous hydration have been shown to prevent contrast‐induced nephropathy (CIN) in patients with chronic renal failure undergoing computed tomography scan, who receive low doses of intravenous contrast. Whether the use of prophylactic acetylcysteine can decrease the incidence of CIN when larger doses of contrast are used remains to be determined. We sought to evaluate whether the prophylactic administration of acetylcysteine plus intravenous hydration is superior to intravenous hydration alone in prevention of CIN in patients with chronic renal failure undergoing cardiac catheterization and receiving moderate to high doses of intravenous contrast (> 1 cc/kg). Seventy‐three consecutive patients with renal insufficiency who received intravenous hydration and 600 mg of acetylcysteine twice a day 24 hr before and the day of the cardiac catheterization were compared with 106 consecutive patients who received hydration alone. Baseline and 48‐hr serum creatinine concentrations were compared between the two groups before and after cardiac catheterization. Multivariate and univariate analysis were performed to assess the effects of acetylcysteine and other clinical variables in the change of serum creatinine after the procedure. Both groups had comparable clinical characteristics and received similar volumes of intravenous hydration. The volume of contrast used was similar for the two groups (2.2 ± 1.7 vs. 2.3 ± 1.5 cc/kg; P = 0.67). A mean change in serum creatinine of 0.17 ± 0.54 mg/dl for the acetylcysteine group vs. 0.19 ± 0.40 mg/dl for the control group (P = 0.77) was observed at 48 hr. The incidence CIN was 13% in the acetylcysteine vs. 12% in the control group (P = 0.84). Acetylcysteine, whether analyzed with multivariate or univariate analysis, failed to demonstrate a significant effect in the change of serum creatinine after cardiac catheterization. In patients with chronic renal insufficiency, acetylcysteine in a dose of 600 mg twice a day before and after cardiac catheterization, along with intravenous fluids, is as effective as fluids alone in the prevention of CIN when moderate to high doses of contrast are used. Cathet Cardiovasc Intervent 2003;58:336–341.

Intracoronary adenosine administered during percutaneous intervention in acute myocardial infarction and reduction in the incidence of 'no reflow' phenomenon

Percutaneous intervention in acute myocardial infarction has been associated with a high incidence of “no reflow,” ranging from 11% to 30%, with an increased risk of complications. The role of intracoronary adenosine for the prevention of this phenomenon has not been evaluated fully. We studied the procedural outcomes of 79 patients who underwent percutaneous intervention in the context of acute myocardial infarction. Twenty‐eight patients received no intracoronary adenosine, and 51 received intracoronary adenosine boluses (24–48 μg before and after each balloon inflation). Eight patients who were not given adenosine experienced no reflow (28.6%) and higher rates of in‐hospital death, while only three of 51 patients (5.9%; P =0.014) in the adenosine group experienced no reflow. No untoward complications were noted during adenosine infusion. Intracoronary adenosine bolus administration during percutaneous intervention in the context of acute myocardial infarction is easy and safe and may significantly lessen the incidence of no reflow, which may improve the outcome of this procedure. Cathet. Cardiovasc. Intervent. 51:27–31, 2000.

Adenosine use during aortocoronary vein graft interventions reverses but does not prevent the slow-no reflow phenomenon.

Slow or no reflow (SNR) complicates 10–15% of cases of percutaneous intervention (PI) in saphenous vein bypass graft (SVG). To date there have been limited options for the prevention and treatment of this common and potentially serious complication. We evaluated the procedural outcome of 143 consecutive SVG interventions. We compared patients who received pre‐intervention intra‐graft adenosine boluses with those who did not. In addition we examined the efficacy of adenosine boluses to reverse slow‐no reflow events. Angiograms were reviewed and flow graded (TIMI grade) by film readers blinded to the use of any intraprocedural drug or clinical history. Seventy patients received intragraft adenosine boluses before percutaneous intervention (APPI), 73 received no preintervention adenosine (NoAPPI). There were no significant angiographic differences between the two groups at baseline. A total of 20 patients experienced SNR. The incidence of SNR was similar in the two groups (APPI = 14.2% vs. NoAPPI = 13.6%, P = 0.9). SNR was treated with repeated, rapid boluses (24 μg each) of intra‐graft adenosine. Reversal of SNR was observed in 10 of 11 patients (91%) who received high doses of adenosine (≥5 boluses, mean 7.7 ± 2.6) and in 3 of 9 (33%) of those who received low doses (<5 boluses, mean 1.5 ± 1.2). Final TIMI flow was significantly better in the high dose than in the low dose group (final TIMI 2.7 ± 0.6 vs. 2 ± 0.8, P = 0.04). No significant untoward complications were observed during adenosine infusion. These findings suggest that SNR after PI in SVG is not prevented by pre‐intervention adenosine, but it can be safely and effectively reversed by delivery of multiple, rapid and repeated boluses of 24 μg of intra‐graft adenosine. Cathet. Cardiovasc. Intervent. 51:394–399, 2000.

High Prevalence of Myocardial Perfusion Abnormalities on Positron Emission Tomography in Asymptomatic Persons With a Parent or Sibling With Coronary Artery Disease

Background —We hypothesized that asymptomatic persons with a parent or sibling with coronary artery disease (CAD) have myocardial perfusion defects on positron emission tomography (PET) as markers of early CAD. Methods and Results —After medical and family histories were recorded, 90 subjects underwent rest-dipyridamole cardiac PET perfusion imaging, including 18 index cases (a subject with CAD documented by PET and arteriography), 32 asymptomatic adults without known CAD who had a parent or sibling with CAD among these index cases, 30 asymptomatic subjects with comparable coronary risk factors without CAD or a family history of CAD, and 10 volunteer control subjects with no risk factors and no family history. PET perfusion images were quantified with automated software for size of abnormalities as percent of the cardiac image outside 95% CIs of normal controls and for severity as the lowest quadrant average relative activity. Of asymptomatic subjects with a parent or sibling with CAD (first-degree relatives), 50% had dipyridamole-induced myocardial perfusion defects that involved ≥5% of the cardiac image outside normal 95% CIs with or without other risk factors. The size of perfusion defects was larger in first-degree relatives than in control subjects (11±13% versus 1±1%, P =0.02) and larger than in asymptomatic subjects with comparable risk factors but no family history of CAD (11±13% versus 5±6%, P =0.02). Conclusions —This study documents the presence of quantitative, statistically significant, dipyridamole-induced myocardial perfusion abnormalities on PET in 50% of asymptomatic persons with a parent or sibling with CAD, independent of other risk factors, indicating preclinical coronary atherosclerosis.

Outcome of access site in patients treated with platelet glycoprotein IIb/IIIa inhibitors in the era of closure devices

The most consistent procedural predictor of vascular access site complications thus far has been the intensity and duration of anticoagulant therapy during and after percutaneous coronary interventions (PCI). Several devices have been developed to aid in the closure of the femoral arteriotomy. This report describes the clinical outcome of unsuccessful deployment of femoral closure devices in a cohort of 285 consecutive patients who underwent PCI and were treated with platelet glycoprotein (GP) IIb/IIIa inhibitors. Manual femoral artery compression was used in 123 patients, Perclose in 123 patients, and AngioSeal in 39 patients. Successful homeostasis was achieved in 98.4% of patients who received manual compression, in 91.9% of the Perclose‐sealed arteriotomy, and in 84.6% of patients who received the AngioSeal closure device (P = 0.004). The incidence of vascular complications after successful deployment was 9%. Patients not achieving hemostasis with closure device or 1° manual compression developed complications in the majority of cases (> 80%; P < 0.05). By multivariate analysis (with adjustment for baseline differences), the use of AngioSeal closure device was found to be an independent risk factors leading to primary deployment failure and all access site complications (OR 2.97; 95% CI 1.5–6.0; P = 0.006). In summary, failed hemostasis by artery closure devices in patients undergoing PCI who are treated with GP IIb/IIIa inhibitors is associated with significant vascular complications. AngioSeal may be associated with a higher failure rate, while manual compression and Perclose seem to be more effective with a lower complication rate. Cathet Cardiovasc Intervent 2003;58:1–5.

The dilemma of success: Percutaneous coronary interventions in patients ≥ 75 years of age - Successful but associated with higher vascular complications and cardiac mortality

Elderly patients are increasingly referred to percutaneous coronary interventions (PCIs). Recent reports suggest complications rates are declining in the elderly. We sought to determine whether procedural and in‐hospital outcomes are different in patients aged ≥ 75 years undergoing nonemergent PCI as compared to patients age < 75 years. The outcome of 266 consecutive patients age ≥ 75 years undergoing nonemergent PCI was compared to that of 1,681 consecutive patients age < 75 years. Compared with younger patients, greater proportions of elderly patients were women and had a history of hypertension, peripheral vascular disease, and cerebral vascular events. Elderly patients had more extensive coronary involvement. Procedural success was similar in both groups (94%). The in‐hospital cardiac death rate was significantly higher in the elderly patients (2.3% vs. 0.7%; P = 0.03). Aged patients also had a significantly higher incidence of vascular and bleeding complications. Blood transfusion was required more often in the elderly group (4.5% vs. 2.6%; P = 0.07). The hospitalization length was significantly higher in the elderly group (4.1 ± 6.0 vs. 2.5 ± 4.3 day; P = 0.0004). By multivariate logistic regression (adjusted for baseline clinical and angiographic variables), age ≥ 75 years was found to be an independent predictor of in‐hospital cardiac death (odds ratio = 3.9; 95% CI = 1.3–11.5; P = 0.015). Although PCI is technically successful in patients aged ≥ 75 years; it is associated with more acute cardiac and vascular complications and higher in‐hospital cardiac mortality. Cathet Cardiovasc Intervent 2003;59:195–199.

Effects of clopidogrel pretreatment before percutaneous coronary intervention in patients treated with glycoprotein IIb/IIIa inhibitors (abciximab or tirofiban)

T clinical efficacy and safety of clopidogrel pretreatment in addition to glycoprotein (GP) IIb/IIIa antagonists during percutaneous coronary intervention (PCI) is unknown. This study compares the in-hospital clinical outcome of patients who received clopidogrel pretreatment before PCI with that in patients who did not receive it as adjunctive antiplatelet therapy to GP IIb/IIIa antagonists. • • • Data were collected from the Memorial Hermann Heart Center Interventional Cardiology database. We examined a consecutive series of 299 patients undergoing PCI. All patients received GP IIb/IIIa inhibitor therapy in the form of abciximab or tirofiban. Use and type of GP IIb/IIIb antagonists was at the discretion of the operator. Abciximab was given as a bolus dose of 0.25 mg/kg body weight followed by continuous infusion of 10 g/min for 12 hours. Tirofiban was given as a loading dose of 0.4 g/kg/min for 30 minutes followed by a maintenance dose of 0.1 g/kg/min for 12 to 24 hours after the procedure. All patients were taking aspirin and received a heparin bolus to achieve an activated clotting time between 250 and 300 seconds. Patients presenting to the catheterization laboratory with a developing myocardial infarction (MI) for a primary or rescue angioplasty were excluded. Patients were divided into 2 groups: those who received clopidogrel pretreatment before PCI (starting within 5 days before PCI or a loading dose of 300 mg the morning of the day of the procedure at the discretion of the primary operator, group I), and those who received aspirin alone (group II) with clopidogrel (300 mg loading dose and 75 mg/day for 1 month) given after stent deployment. Therapy with clopidogrel (75 mg/day) was continued for 1 month in both groups if the stent was deployed during the procedure. Coronary angioplasty and intracoronary stent implantation were performed using standard percutaneous techniques. Balloon size was selected to match the reference vessel diameter obtained from on-line angiographic analysis (1.1:1 balloon/artery ratio). Different types of stents were used (excluding open coil type). After stent implantation, high-pressure balloon dilatation was performed for angiographic optimization. Intravascular ultrasonography–guided coronary stenting was not performed in most patients. Each operator relied on his own judgment or on other objective measurements, such as online quantitative coronary angiography, to assess PCI results. On completion of the procedure, patients were moved to a monitored unit and the arterial sheath was removed. Successful PCI was defined as final residual stenosis within the treated lesion of 20%, with achievement of Thrombolysis In Myocardial Infarction grade 3 flow, without in-lab occurrence of death, MI, or a complication requiring immediate coronary revascularization. A major adverse cardiac event was defined as any 1 of the following: (1) Q-wave or non–Q-wave MI, (2) need for urgent repeat target vessel revascularization, or (3) cardiovascular death that occurred during the period of hospitalization after the index coronary procedure. Postprocedural MI was defined as the occurrence of typical ischemic chest pain of 30 minutes duration with a creatine kinase elevation of 3 times the upper limit of normal with an associated increase in the MB fraction. There was no routine protocol for acquisition of postprocedure creatine kinase. All postprocedural cardiac enzymes were obtained for suspected recurrent myocardial ischemia, manifested by recurrent postprocedural chest pain, hemodynamic instability, or new electrocardiographic changes of ischemia. Urgent target vessel revascularization was defined as a repeat PCI or coronary artery bypass grafting of the index artery due to presumed recurrent ischemia manifested by recurrent angina, arrhythmias, or hemodynamic compromise. Adverse effects of therapy were recorded and compared between the 2 groups. These consist of major bleeding and thrombocytopenia. Major bleeding was defined as bleeding requiring transfusion of blood products or precipitating hemodynamic compromise. Intracerebral hemorrhage of any extent was considered a major adverse effect of therapy. Thrombocytopenia was defined as platelet count 100,000/mm. Chi-square and Fischer exact tests were used for analysis of categorical variables when appropriate, and Student t testing was used for analysis of continuous variables. Multivariate logistic regression analysis was performed to determine significance of variables related to an in-hospital major adverse cardiac From the Cardiology Division, University of Texas Medical School and Hermann Heart Center, Memorial Hermann Hospital, Houston, Texas. Dr. Rosales’ address is: Division of Cardiology, University of Texas Health Science Center-Houston, PO Box 20708, Houston, Texas 77225-0708. Manuscript received March 29, 2001; revised manuscript received and accepted May 30, 2001.